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Broadening the scope of biocatalytic C–C bond formation

Nature Reviews Chemistry volume 4, pages 334–346 (2020)Cite this article

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Abstract

Enzymes exercise impeccable control over chemoselectivity, site selectivity and stereoselectivity in reactions they mediate, such that we have witnessed a surge in the development of new biocatalytic methods. Although carbon–carbon (C–C) bonds are the central framework of organic molecules, biocatalytic methods for their formation have largely been limited to a select few lyase enzymes. Thus, despite several decades of research, there are not many biocatalytic C–C-bond-forming transformations at our disposal. This Review describes the suite of enzymes available for highly selective, biocatalytic C–C bond formation. We discuss each class of enzyme in terms of native activity, alteration of this activity through protein or substrate engineering, and its utility in abiotic synthesis.

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Fig. 1: Engineering enzymes for organic synthesis.
Fig. 2: Biocatalytic alkylation using activated electrophilic coenzymes or alkyl donors.
Fig. 3: Biosynthetic and biocatalytic ring-closing reactions.
Fig. 4: Site-selective acetylation of resorcinol derivatives catalysed by an acyltransferase.
Fig. 5: Intermolecular oxidative coupling reactions in nature.
Fig. 6: Cyclization reactions catalysed by native and engineered enzymes.
Fig. 7: Engineering non-natural carbene transferases for C–C bond formation.

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Acknowledgements

The authors are grateful for support from the National Institutes of Health (R35 GM124880 and T32 GM008353).

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  1. Program in Chemical Biology, University of Michigan, Ann Arbor, MI, USA

    Lara E. Zetzsche & Alison R. H. Narayan

  2. Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA

    Lara E. Zetzsche & Alison R. H. Narayan

  3. Department of Chemistry, University of Michigan, Ann Arbor, MI, USA

    Alison R. H. Narayan

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L.E.Z. and A.R.H.N. contributed to the writing and editing of the article.

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Glossary

Lyases

A class of enzymes characterized by the ability to break or form a new chemical bond using mechanisms other than hydrolysis or oxidation.

Atroposelective

A preference for the formation of a specific stereoisomer (atropisomer) whose axis of chirality results from hindered rotation around a single bond that results in only one of two possible stable conformations.

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Zetzsche, L.E., Narayan, A.R.H. Broadening the scope of biocatalytic C–C bond formation. Nat Rev Chem 4, 334–346 (2020). https://doi.org/10.1038/s41570-020-0191-2

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